Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone morphogenetic protein-2 (BMP-2) inhibits terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T., Rosen, V., Wozney, J. M., Fujisawa-Sehara, A., and Suda T. (1994) J. Cell Biol. 127, 1755-1766). In the present study, we examined the possible involvement of Smad proteins, vertebrate homologues of Drosophila Mothers against decapentaplegic, in the BMP effects on the differentiation of C2C12 myoblasts. C2C12 cells expressed Smad1, Smad2, Smad4, and Smad5 mRNAs, and expression levels were not altered by treatment with BMP-2 or TGF-beta1. When Smads were transiently transfected into C2C12 cells, both Smad1 and Smad5 induced alkaline phosphatase (ALP) activity and decreased the activity of myogenin promoter/chloramphenicol acetyltransferase (myogenin-CAT) without BMP-2. When C-terminal-truncated Smad1 and Smad5 were transfected into constitutively active BMP receptor type IB (BMPR-IB)-expressing C2C12 cells, BMP signals were blocked, resulting in an increase in myogenin-CAT activity. On the other hand, Smad1 and Smad5 decreased myogenin-CAT activity but did not induce ALP activity in MyoD-transfected NIH3T3 fibroblasts. These results suggest that both Smad1 and Smad5 are involved in the intracellular BMP signals which inhibit myogenic differentiation and induce osteoblast differentiation in C2C12 cells, and that the conversion of the two differentiation pathways is regulated independently at a transcriptional level.
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PMID:Smad1 and smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts. 929 54

Mothers against decapentaplegic-related proteins (Smads) are essential intracellular components for the signal transduction of transforming growth factor-beta (TGF-beta) family members. Smad1 mediates bone morphogenetic protein (BMP) signals, whereas Smad2 functions downstream of TGF-beta. TGF-beta is expressed in osteoblastic cells and acts as an autocrine and/or paracrine factor in regulation of osteoblastic functions. In this study, we examined the levels and functions of Smad2 in osteoblastic cells. Smad2 mRNA expression was hardly detectable by Northern blot analysis in an osteoblast-like cell line, ROS17/2.8, as well as in primary rat calvaria (PRC) cells. Overexpression of Smad2 gene enhanced endogenous Smad4 gene expression in both ROS17/2.8 and PRC cells, while Smad3 levels were not altered. Smad2 overexpression suppressed osteocalcin mRNA expression in ROS17/2.8 cells. Furthermore, Smad2 overexpression also suppressed transcriptional activity of the 1-kilobase pair osteocalcin gene promoter, which was linked to chloramphenicol acetyltransferase reporter gene in both ROS and PRC cells. Since core binding factor A1 (CBFA1) is involved in osteocalcin gene expression, we further examined CBFA1 expression in the Smad2-overexpressing ROS17/2.8 and PRC cells. The levels of CBFA1 mRNA were suppressed by the overexpression of Smad2 by about 50% in both ROS17/2.8 and PRC cells. TGF-beta treatment enhanced Smad4 expression in PRC cells, and this TGF-beta effect was blocked by the cotreatment with BMP, indicating that TGF-beta signaling pathway is interfered by BMP. These data indicate that Smad2 regulates Smad4 specifically and that CBFA1 gene is one of the downstream targets of Smad2.
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PMID:Smad2 overexpression enhances Smad4 gene expression and suppresses CBFA1 gene expression in osteoblastic osteosarcoma ROS17/2.8 cells and primary rat calvaria cells. 981 98